title: Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system.
abstract: The arylhydrocarbon receptor (AhR) is a ligand-dependent transcription factor mediating the adverse effects of dioxins. Although cross-talk of dioxins with estrogen and androgen signaling pathways are well described, the underlying molecular mechanisms have been largely elusive. Recent studies showed that modulation of estrogen/androgen signaling by dioxins is exerted in part through direct association of AhR with estrogen (ER) or androgen (AR) receptors. Agonist-bound AhR and ERα work as a functional unit to regulate expression of target genes. In addition to such genomic actions, AhR mediates non-genomic actions of AhR-ligands through the assembly of a CUL4B-based ubiquitin ligase complex and promotes the degradation of ERα and AR. These findings reveal the roles of the ubiquitin system in sensing and biological response to environmental chemicals, in which AhR acts as a ubiquitin ligase component to enhance the destruction of specific substrates.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ohtake
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Kaname
authors.initials: K
authors.lastname: Kawajiri
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D004147:Dioxins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D020239:Receptor Cross-Talk / Q000187:drug effects*; D011944:Receptors, Androgen / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000728:Androgens; D004147:Dioxins; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D011960:Receptors, Estrogen; D025801:Ubiquitin; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases